Dissertation a Phytochemical and Pharmacological Study of Te

CHAPTER 1: GENERAL INTRODUCTION The utilisation of plants in the treatment of certain human diseases is evidence of man’s ingenuity. The contribution of these plants to the therapeutic arsenal in the fight against disease dates back several centuries, and has, to a certain extent, been documented by the ancient Chinese, Indian and North African civilisations. Currently, traditional medicine is widely practiced, especially in developing countries. This is a result of primary health care facilities being unable to manage the number of patients requiring aid, the high cost of Western pharmaceuticals and health care, as well as the fact that traditional health care is highly sought after in terms of certain cultural elements in the lives of these individuals within these societies (Taylor et al ., 2001). In southern Africa, a large proportion of the population still uses traditional remedies. More than 700 plant species are being traded for medicinal purposes throughout South Africa, in the informal medicinal plant market (Dold and Cocks, 2002). This vast usage of and great dependence on traditional plants as the preferred form of health care is aided by the fact that most of these plants are widely available and affordable, and additionally encompasses practices based on the social-cultural norms and religious beliefs. It is evident that, even though scientific advances have been made in our quest to understand the physiology of the body, biotechnology and the treatment of disease, natural products remain a crucial component of the comprehensive health care strategy for the future (Patwardhan, 2005). The World Health Organization (WHO) defines traditional medicine as the “diverse health practices, approaches, knowledge and beliefs incorporating plant-, animal- and/or mineral- based medicines, spiritual therapies, manual techniques and exercises applied singularly or in combination to maintain well-being, as well as to treat, diagnose, or prevent illness”. It is clear, however, that there is a need to validate the information through an organised infrastructure for it to be used as an effective therapeutic means, either in conjunction with existing therapies, or as a tool in novel drug discovery. Traditional medicine utilises biological resources and the indigenous knowledge of traditional plant groups, the latter being conveyed verbally from generation to generation. This is closely linked to the conservation of biodiversity and the related intellectual property rights of indigenous people (Timmermans, 2003). 35 Although it is these traditional medicines that provided the link between medicine and natural products, it was not until the 19 th century that active compounds were isolated and principles of medicinal plants identified (Phillipson, 2001). The Greek physician Dioscorides ( AD 70) compiled an extensive listing of medicinal herbs and their virtues. This was originally written in Greek, and later translated into Latin as De Materia Medica, and remained the authority in medicinal plants for over 1500 years (Mendonça-Filho, 2006). Another Greek physician, Galen ( AD 129-200), devised the pharmacopoeia describing the appearance, properties and use of many plants of his time. It was the discovery of medicines such as those listed in Table 1.1 that sparked an interest in the study of plants as medicinal agents; with the isolation of morphine from opium by Serturner (1805) being the start of natural product chemistry (Patwardhan et al ., 2004). Table 1.1: Drugs derived from plants, their clinical uses and sources (Fabricant and Farnsworth, 2001). Drug Action or clinical use Plant source Atropine Anticholinergic Atropa belladona Colchicine Antitumour, antigout agent Colchicum autumnale Digitoxin Cardiotonic Digitalis purpurea Emetine Emetic, amoebicide Cephaelis ipecacuanha Morphine Analgesic Papaver somniferum Pilocarpine Parasympathomimetic Pilocarpus jaborandi Quinine Antimalarial Cinchona ledgeriana Despite the discovery of natural products from higher plants, the interest of chemists, pharmaceutical scientists and pharmacologists turned to the production of synthetic compounds. In the late 19 th century, research was focused mainly on the modification of natural products, in an attempt to enhance biological activity, to increase selectivity and to decrease toxicity and side effects. Aspirin is one such example and was the earliest of these modified natural products. In more recent years, however, industry has once again turned its interests to natural product research (Phillipson, 2001). This is as a result of the 36 development of drug-resistant micro-organisms, side effects of modern drugs and emerging diseases for which no medicine is available. 1.1 Ethnopharmacological research The study of plants used in traditional medicine requires the effective integration of information on chemical composition of extracts, pharmacological activities of isolated compounds, as well as indigenous knowledge of traditional healers. The acquisition of ethnobotanical information remains an empirical aspect in any such study (Soejarto, 2005). The process of isolating and identifying lead compounds from a complex mixture requires a number of specific resources, including comprehensive knowledge, specialised equipment and skill. The urgency of the discovery of new agents is a result of impenetrable factors that come into play, including the emergence of new killer diseases, known antimicrobial drug-resistance, the inefficiency of synthetic drug discovery and the high cost of bringing to market a single drug. A shift towards natural product research, which is further driven by remarkable advances in plant extract technology, biotechnology and analytical chemistry, is therefore inevitable. There is a great need and ethical obligation to accurately document investigative findings on plants used for health purposes. This will additionally aid in the efficient preservation and conservation of traditional knowledge, thereby preventing the further disappearance of indigenous systems of medicine, which may potentially benefit society in general. According to the Southern African Trade Directory of Indigenous Natural Products, more than 1 000 species of plants are used traditionally in southern Africa (Izimpande, 2005) of which the genus Commiphora is one. 1.2 An introduction to the family Burseraceae and genus Commiphora 1.2.1 The family: Burseraceae The Burseraceae is composed of both trees and shrubs of tropical and sub-tropical geographical distribution (Watson and Dallwitz, 1992). The bark of the trees are known mostly for producing fragrant resins of economic, medicinal and cultural value 37 (Langenheim, 2003), and for baring essential oils. The Burseraceae consists of approximately 700 species from 18 genera. This family is divided into three tribes, namely Canarieae, Protieae and Bursereae, each distributed pantropically across a broad range of low-elevation, frost-free habitats including rainforest, dry deciduous forest and desert (Weeks et al ., 2005). This classification is based exclusively upon their fruit structure. In a study by Clarkson et al . (2002), the tribal relationships within the Burseraceae were revealed by the phylogeny depicted in Figure 1.1. This was determined through the sampling of chloroplast rps 16 intron sequences (ribosomal protein genes) from 13 species of 11 genera within the Burseraceae, rooting their analysis with several genera in the Anacardiaceae, a family closely resembling the Burseraceae and with which it has been closely allied traditionally. The Burseraceae is one of nine flowering plant families belonging to the order Sapindales that comprise the monophyletic group (5,700 species), whos first known fossils appear in Europe ca. 65 million years ago (Ma). Two of the three tribes, namely Canarieae and Protieae, were determined to be monophyletic, while the Burserae were shown to be polyphyletic. Commiphora has several species in Africa and at least one species ( Commiphora leptophloeos ) in South America. A Gondwanan origin of the family was assumed and the separation of Africa and South America (95 - 100 Ma) was used to date disjunct Commiphoras common ancestor and thereby calibrate the difference in times across the family (Becerra, 2005). The hypothesis of the Gondwanan origin needed to be refined. The molecular phylogenies of the Burseraceae were based on nuclear and chloroplast DNA data for 13 of the 18 genera. A map of the Early Eocene continents and their relative positions helps illustrate the expansive distribution of the Burseraceae (Figure 1.2). The Early Eocene age of the Burserinae and its broadly North American origin implicates at least one migration event to the Old World to explain the African, Madagascar, and Indian distributions of Commiphora species. The data obtained supported a North American Paleocene origin for the Burseraceae, followed by the dispersal of ancestral lineages to North America and the Southern Hemisphere. Commiphora appears to have dispersed and radiated within continental Africa approximately 44 Ma, during the Middle Eocene. The spread of Commiphora to India appears to have occurred in relatively recent geologic times, approximately 5.0 Ma (Weeks et al ., 2005). 38 Trattinnickia – NW Dacryodes – OW Canariae Sentiria – OW Triomma – OW Garuga – OW Bursereae Boswellia – OW s ubtribe Boswelliniae Protium sp. 1 – NW Protium sp. 2 – OW Protieae Protium sp. 3 – OW Crepidospermum – NW Bursera – NW Bursereae Commiphora – OW subtribe Burserinae Beiselia – NW subtribe

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